Content uploaded by Bruce R King
Author content
All content in this area was uploaded by Bruce R King on Dec 18, 2014
Content may be subject to copyright.
Available via license: CC BY-NC 4.0
Content may be subject to copyright.
Bubble formation occurs in insulin
pumps in response to changes in
ambient temperature and atmospheric
pressure but not as a result of vibration
Prudence E Lopez,
1,2,3
Bruce R King,
1,2,3
Peter W Goss,
4
Ganesh Chockalingam
5
To cite: Lopez PE, King BR,
Goss PW, et al. Bubble
formation occurs in insulin
pumps in response to
changes in ambient
temperature and atmospheric
pressure but not as a result
of vibration. BMJ Open
Diabetes Research and Care
2014;2:e000036.
doi:10.1136/bmjdrc-2014-
000036
Parts of this study were
presented in poster form at
the 2012 Advanced
Technologies and Treatments
for Diabetes Conference,
Barcelona, Spain, February
2012.
Received 28 April 2014
Revised 17 July 2014
Accepted 29 July 2014
For numbered affiliations see
end of article.
Correspondence to
Dr Bruce R King;
bruce.king@hnehealth.nsw.
gov.au
ABSTRACT
Introduction: Bubble formation in insulin pump
giving sets is a common problem. We studied change
in temperature, change in atmospheric pressure, and
vibration as potential mechanisms of bubble formation.
Methods: 5 Animas 2020 pumps with 2 mL
cartridges and Inset II infusion systems, 5 Medtronic
Paradigm pumps with 1.8 mL cartridge and Quickset
and 3 Roche Accu-chek pumps with 3.15 mL
cartridges were used. Temperature study: insulin
pumps were exposed to a temperature change from 4°
C to 37°C. Pressure study: insulin pumps were taken
to an altitude of 300 m. Vibration study: insulin pumps
were vigorously shaken. All were observed for bubble
formation.
Results: Bubble formation was observed with changes
in temperature and atmospheric pressure. Bubble
formation did not occur with vibration.
Discussion: Changes in insulin temperature and
atmospheric pressure are common and may result in
bubble formation. Vibration may distribute bubbles but
does not cause bubble formation.
INTRODUCTION
At our centre, patients using insulin pump
therapy frequently report bubble formation
in insulin cartridges and tubing. Bubble for-
mation is a concern to patients and families
who often fear that non-delivery of insulin
will result. The causes of bubble formation in
insulin cartridges and tubing have not previ-
ously been studied.
Case study
A child with type 1 diabetes mellitus managed
with a Medtronic Veo insulin pump lived on a
remote farm where there were commonly
large temperature changes through the day
(10–35°C). The child travelled 10 km to
school on a rough dirt tract that included a
600 m climb. The family frequently found
bubbles in the insulin pump tubing and cart-
ridge on arrival at school and were concerned
about the impact of the bubbles on insulin
delivery. In our clinical practice, it is not
uncommon for patients and their families to
report bubble formation in insulin pump car-
tridges and tubing.
We studied physical factors that may be
involved in bubble formation, including
change in pressure, change in temperature,
and vibration.
METHODS
Only mechanical equipment was used in
these studies, therefore ethics approval was
not sought.
Five Animas 2020 pumps with 2 mL car-
tridges (IR1200/2020; Animas, West Chester,
Pennsylvania, USA) and Inset II infusion
systems (Animas), five Medtronic Paradigm
pumps with 1.8 mL cartridge and Quickset
(Medtronic, Minneapolis, Minnesota, USA),
and three Roche Accu-chek spirit pumps
with 3.15 mL cartridge (F.Hoffman-La
Roche, Basel, Switzerland) and Inset II infu-
sion sets (Animas) were used.
The cartridges were filled with aspart
insulin (NovoNordisk, Bagsvaerd, Denmark)
and loaded into the pumps as described in
the product literature.
Temperature study
We used Henry’s law to model bubble forma-
tion from saline that occurs as the tempera-
ture changes
1
(see figure 1).
Six cartridges and tubing systems (three
Animas 2 mL cartridges and three Roche
Key messages
▪Bubble formation in insulin pumps is common
and may cause anxiety for patients and families.
▪Changes in ambient temperature and atmos-
pheric pressure may result in bubble formation
in insulin pumps.
▪Vibration of an insulin pump does not result in
bubble formation.
BMJ Open Diabetes Research and Care 2014;2:e000036. doi:10.1136/bmjdrc-2014-000036 1
Open Access Research
3.15 mL cartridges) were filled with aspart insulin at
4°C. Six insulin pumps (three Animas 2020 and three
Roche Accu-chek) were kept at room temperature. The
insulin cartridges and tubing were taken out of the
refrigerator and loaded into the insulin pumps. The
insulin pumps containing the cartridges and infusion
sets were placed into an oven (Thermoline Labtech,
Sydney, Australia) at 37°C for 3 h. The insulin pumps
and cartridges were then removed from the oven and
examined for bubble formation. The experiment was
repeated five times.
Pressure study
Four Medtronic insulin pumps and microtubules were
fixed on a board. They were taken to 300 m in the
Eureka Tower in Melbourne, Australia. The atmospheric
pressure change was −22 mm Hg. The pump cartridges
and microtubules were observed for bubble formation.
The experiment was repeated three times.
Vibration study
Thirty Roche 3.15 mL cartridges were loaded with aspart
insulin and then individually placed on a S.E.M. Vor-Mix
agitator (S.E.M., Adelaide, Australia) for 10 s at
1500 rpm. The syringe was orientated horizontally (vibra-
tion force transverse across the syringe), vertically (vibra-
tion force longitudinally along the syringe), and in the
center of the vortex machine (rotational force through
the syringe). After each vibration event (10 s duration)
the cartridges were examined for bubble formation.
RESULTS
Temperature study
When the cartridges were taken out of the refrigerator
(4°C), placed into the pump at room temperature, and
placed into an oven (37°C), bubble formation was
observed after the cartridges were removed from the
insulin pumps. Bubbles were found in the 2 and
3.15 mL cartridges and in the tubing sets (see figure 2).
Pressure study
During the 300 m ascent, the pressure decreased by
22 mm Hg and bubble formation was observed in the
pump cartridges and tubing.
Vibration study
Despite vigorously agitating the insulin pump cartridges,
bubble formation was not observed in any cartridges or
tubing.
DISCUSSION
We demonstrated bubble formation in the tubing and
syringe of insulin pumps with an increase in tempera-
ture and a decrease in ambient pressure, but not with
vibration.
Figure 1 Mathematical modeling of bubble formation in
insulin pump cartridges (3 mL solid line, 2 mL dotted line, and
1.8 mL dashed line) and lines during an increase in
temperature from 4°C to 37°C. Henry’s law (1) was used to
graph the predicted bubble formation in insulin as the
temperature changes between 4°C and 37°C.
Figure 2 Bubbles present in an insulin pump cartridge and
line following an increase in temperature from 4°C to 37°C.
The insulin cartridge and line containing aspart insulin was
cooled to 4°C in a fridge and then moved to an oven at 37°C.
2BMJ Open Diabetes Research and Care 2014;2:e000036. doi:10.1136/bmjdrc-2014-000036
Clinical care/education/nutrition/psychosocial research
Henry’s law predicts that bubbles will form as the tem-
perature of the insulin rises.
1
In hot climates, it is recom-
mended that insulin is refrigerated for storage.
23
Often,
the insulin is not warmed prior to use. This may result
in bubble formation as the temperature of the insulin
increases. The magnitude of temperature change
required to produce bubble formation is currently
unknown and would warrant further study. As ambient
pressure decreases, Henry’slaw
1
predicts that bubbles
will form. King et al
4
have previously demonstrated that a
50 mm Hg decrease in ambient pressure causes bubble
formation. A change in ambient pressure may occur in
many situations, such as taking an elevator or driving up
a hill and could potentially result in bubble formation.
This study demonstrated that bubble formation can
occur with a 22 mm Hg decrease in ambient pressure.
Vibration of an insulin pump may occur in many situa-
tions, such as when the insulin pump is dropped,
driving on a rough road, or the pump is shaken. Our
study did not demonstrate bubble formation as a result
of vigorous vibration. Patients and their families may be
reassured that dropping or shaking an insulin pump is
unlikely to result in bubble formation. However, if there
are bubbles already present in the syringe then vibration
could move bubbles so they could enter the tubing.
It is currently unknown whether bubble formation in
insulin pumps has any effect on insulin delivery by the
pump. Temperature changes could be predicted to alter
insulin delivery due to thermal expansion and contrac-
tion.
5
Alterations in pressure could also be expected to
result in changes in the rate of insulin delivery.
6
King
et al
4
demonstrated that pressure changes during airline
flight caused alterations in the rate of insulin delivery.
Changes in insulin delivery due to environmental factors
may occur independently of bubble formation. Such
engineering principles are well known to insulin pump
manufacturers, and modern insulin pumps have been
designed to avoid changes in insulin delivery in response
to known environmental phenomena. We anticipate that
such design features would be common to all insulin
pumps; however, we were unable to perform the tem-
perature study, pressure study, and vibration study with
insulin pumps from each manufacturer. Further studies
are required to determine the effect of bubble forma-
tion on delivery of insulin across a range of insulin
pumps.
Parents of children with type 1 diabetes often report
feeling stressed. Insulin pump therapy has been asso-
ciated with a reduction in parenting stress felt by carers
of children with type 1 diabetes.
7
Anecdotally, however,
technical issues surrounding insulin pumps may be a
source of anxiety. Technical difficulties with managing
insulin pumps may lead to permanent cessation of
insulin pump therapy.
8
Patients and families are often
concerned about the presence of bubbles as they fear
non-delivery of insulin as the bubbles pass through the
tubing. Currently, the impact of bubble formation on
insulin delivery is unknown. Advising patients and fam-
ilies about the causes of bubble formation may help
them avoid bubble formation and assist with early identi-
fication. This may assist to reduce the already elevated
anxiety levels of patients and families with type 1
diabetes.
Patients using insulin pump therapy should be aware
of the potential for bubble formation in seemingly
innocuous situations. Patients should be encouraged to
warm refrigerated insulin to room temperature prior to
use. If patients encounter an environment where there
is a decrease in ambient pressure, inspection of the cart-
ridge for bubble formation may be warranted. Patients
and families can be reassured that vibration of an
insulin pump is not likely to result in bubble formation.
Further studies to determine the impact of bubble for-
mation on insulin delivery are required to fully inform
clinicians, patients, and families of the importance of
bubble formation.
Author affiliations
1
John Hunter Children’s Hospital, Newcastle, New South Wales, Australia
2
Mothers and Babies Research Group, Hunter Medical Research Institute,
Newcastle, New South Wales, Australia
3
University of Newcastle, Newcastle, New South Wales, Australia
4
Gippsland Paediatric Diabetes Unit, Sale, Victoria, Australia
5
John Hunter Hospital, Newcastle, New South Wales, Australia
Acknowledgements The authors would like to thank the families who kindly
donated their Medtronic and Animas insulin pumps for study purposes, with
no restriction or input into the study purposes. Professor Roger Smith,
Dr Mark Read, Dr John Fitter, and the Mothers and Babies Research Institute,
Newcastle, Australia, provided equipment and expertise.
Contributors BRK designed and coordinated the project, led the analysis,
wrote the manuscript, and reviewed and edited the manuscript and is
guarantor of the work included in the study. PEL, PWG, and GC collected and
analysed data, wrote the manuscript, and reviewed and edited the manuscript.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
Open Access This is an Open Access article distributed in accordance with
the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work non-
commercially, and license their derivative works on different terms, provided
the original work is properly cited and the use is non-commercial. See: http://
creativecommons.org/licenses/by-nc/4.0/
REFERENCES
1. Sander R. Compilation of Henry’s Law constants for inorganic and
organic species of potential importance in environmental chemistry.
Air Chemistry Department Max-Planck Institute of Chemistry Version
3. 1999.
2. NovoRapid Penfill 3 mL Consumer Medicine Information. https://
www.mimsonline.com.au.acs.hcn.com.au/Search/CMI.aspx?
ModuleName=ProductInfo&searchKeyword=novorapid&
PreviousPage=~/Search/QuickSearch.aspx&SearchType=&ID=
53570002_2 (accessed 28 Jan 2013).
3. Humulin Cartridges Consumer Medicine Information. https://www.
mimsonline.com.au.acs.hcn.com.au/Search/CMI.aspx?
ModuleName=ProductInfo&searchKeyword=humulin&
PreviousPage=~/Search/QuickSearch.aspx&SearchType=&ID=
29090002_2 (accessed 28 Jan 2013).
BMJ Open Diabetes Research and Care 2014;2:e000036. doi:10.1136/bmjdrc-2014-000036 3
Clinical care/education/nutrition/psychosocial research
4. King BR, Goss PW, Paterson MA, et al. Changes in altitude cause
unexpected insulin delivery from insulin pumps: mechanisms and
implications. Diabetes Care 2011;34:1932–3.
5. Elert G. The Physics Hypertextbook. http://physics.info/expansion/
(accessed 15 Jul 2014).
6. Bernoulli’s Principle. http://www.princeton.edu/~achaney/tmve/
wiki100k/docs/Bernoulli_s_principle.html (accessed 15 Jul 2014).
7. Streisand R, Swift E, Wickmark T, et al. Pediatric parenting stress
among parents of children with type 1 diabetes: The role of
self-efficacy, responsibility and fear. J Pediatr Psychol
2005;30:513–21.
8. Wheeler BJ, Heels K, Donaghue KC, et al. Insulin pump-associated
adverse events in children and adolescents—a prospective study.
Diabetes Technol Ther 2014. Published online first.
4BMJ Open Diabetes Research and Care 2014;2:e000036. doi:10.1136/bmjdrc-2014-000036
Clinical care/education/nutrition/psychosocial research